JSCO2016: International Session 6 Gynecological Cancer (Uterine Body Cancer and Ovarian Cance

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The 54th Annual Meeting of Japan Society of Clinical Oncology (JSCO2016)

"Renovation of Cancer Medicine in the Mature Society"



International Session 1: Lung Cancer
International Session 2: Colorectal Cancer
International Session 3: Gastric Cancer
International Session 4: Urological Cancer (Prostate and Renal Cancer)
International Session 5: Supportive Care for Adverse Events
International Session 6: Gynecological Cancer (Uterine Body Cancer and Ovarian Cancer)
International Session 7: Central Nervous System Tumor
International Session 8: New Development of Particle Beam Therapy for Cancer
International Session 9: International Cooperation in Radiation Medicine
International Session 10: Recent Advances In Cancer Immunotherapy
International Session 11: Breast Cancer
International Session 12: Pharmacology of Antitumor Agents: New Drug Application (NDA)
International Session 13: Malignant Lymphoma
International Session 14: Palliative Care
International Session 15: Radiation Therapy
International Session 16: Head and Neck Cancer
International Session 17: Skin Cancer (Malignant Melanoma)
International Session 18: Hepato-Biliary and Pancreas Cancers
International Session 19: Leukemia
International Session 20: Ethics for Clinical Research
International Session 21: Esophageal Cancer
International Session 22: Bone and Soft Tissue Tumor
FACO/JSCO Joint Symposium

Abstract Archives (in Japanese)


International Session 6: Gynecological Cancer (Uterine Body Cancer and Ovarian Cancer)


Japan Society of Gynecologic Oncology guidelines 2013 for the treatment of uterine body neoplasms
Kiyoko Kato (Gynecology and Obstetrics, Kyushu University Hospital)
Endometrial cancer is the most common gynecological malignancy in industrialized countries, comprising 4% of all cancer incidences in women, with a lifetime risk of 2-3%. In Japan, its incidence has increased recently. According to the statistics of Center for Cancer Control and information services, National Cancer Center in Japan, it is estimated that 14,763 new uterine cancer cases occurred in 2011 and 2,243 deaths resulting from the disease in 2014. Surgery, chemotherapy, radiation, and hormone therapy are used either alone or sequentially to treat endometrial cancer. To delineate clearly the standard of care for endometrial cancer treatment in Japan, the guidelines for the treatment of endometrial cancer were published in 2006. The second revised version were published in 2009 containing two new sections: the treatment of mesenchymal tumors such as leiomyosarcoma and the treatment of serous and clear-cell adenocarcinoma. The third revised version were published in 2013, comprising nine chapters and nine algorithms. The third revised version mention the clinical significance of pelvic lymph node dissection and para-aortic lymphadenectomy, including variant histologic types, the indications for laparoscopic surgery as the standard treatment, guidelines for post-treatment hormone replacement therapy, clearly differentiate treatment of advanced or recurrent cancer between the initial treatment and the treatment carried out after the primary operation, fertility-sparing therapy for both atypical endometrial hyperplasia and endometrioid adenocarcinoma (corresponding to G1), relapse therapy after fertility-preserving treatment, and newly describe the treatment of trophoblastic disease. I make a commentary on these points.


Guideline for Treatment of Ovarian Cancer including Primary Peritoneal Cancer and Fallopian Tube Cancer Version 2015 edited by the Japan Society of Gynecologic Oncology
Hidetaka Katabuchi (Guideline Committee, Japan Society of Gynecologic Oncology)
In Japan, ovarian cancer is currently the most common cause of death among malignant tumors of the female genital tract. In order to improve the prognosis of ovarian cancer and reduce regional differences of its management, the 1st edition of the Guideline for Treatment of Ovarian Cancer was edited and published by the Japan Society of Gynecologic Oncology in 2004. The 4th edition of the Guideline for Treatment of Ovarian Cancer including Primary Peritoneal Cancer and Fallopian Tube Cancer Version 2015 was published. The major changes in this new edition are as follows: (1) The format has been changed from review to clinical questions (CQ), and the guidelines for optimal clinical practice in Japan are now shown as 41 CQs and answers. (2) The "flow charts" have been improved and placed near the beginning of the guideline. (3) FIGO surgical staging of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was revised in 2014, as was the WHO histological classification of ovarian tumors. Accordingly, this guideline has been revised to be compliant with the new versions of these classifications. (4) Procedures for examination and management of hereditary breast and ovarian cancer have been described. (5) Information on molecular targeting therapy has been added. (6) Guidelines for treatment of recurrent cancer based on tumor markers alone have been described, as well as guidelines for providing hormone replacement therapy after treatment. In this guideline, much of the evidence adopted was obtained from clinical studies performed in Europe, the USA, and Japan. However, some evidence from western countries does not apply in Japan because of differences in background factors between Europe/USA and Japan. Conversely, some treatments used widely in Japan are uncommon in Europe and the USA. In such cases, the current consensus for disease management in Japan is prioritized in this guideline.


Recent results and ongoing European studies in ovarian and endometrial cancer: 2016 update
Cristiana Bruna Sessa (IOSI Bellinzona, CH, European Society of Medical Oncology ESMO, Switzerland)
Cytoreductive surgery is one of the mainstays of treatment in ovarian cancer and its value in platinum sensitive recurrent disease has been assessed in the DESKTOP III (AGO – OVAR OP.4) (NCT 01166737) comparing tumour debulking surgery followed by chemotherapy CT only. The value of primary cytoreductive surgery versus neoadjuvant chemotherapy has been assessed in the CHORUS study performed in UK and Australia (Lancet Oncol. 2016). Still ongoing is the ICON 8 B (INCT 01654146) study, comparing in high-risk patients stage III-IV dose fractionated CT with/without bevacizumab to three weekly CT with bevacizumab following primary surgery or as part of a neoadjuvant approach.
Bevacizumab is still the only approved antiangiogenic compound in combination with standard first line carboplatin/ paclitaxel because of the unfavourable safety profile of the oral antiangiogenic nintedanib as shown in the Phase III AGO-OVAR12 (Lancet Oncol. 2016). Bevacizumab still plays an important role in platinum sensitive recurrent disease and the value of its continuation beyond progression is currently tested in the MITO 16/Mango 2b study (NCT 018 02 749); the value of a combination with platinum versus a combination without platinum in partially sensitive platinum recurrent disease is under evaluation in the INOVATYON study (NCT 0137 9989).
The value of PARP inhibitors as maintenance has been established in BRCA mutated patients with platinum sensitive recurrent disease in the Study 19 with Olaparib (Lynparza), which provided the data for the EMA approval of the indication in 2015, as well as in high-grade serous or germline BRCA mutated patients with niraparib in the recently completed NOVA trial (NCT 081847274). The therapeutic value of single agent PARP inhibitors has been evaluated in platinum sensitive high-grade patients in the ARIEL 2 study with rucaparib (NCT 1891344), of which some preliminary results have been already reported (ASCO 2015).
The ESMO-ESGO-ESTRO consensus conference (CC) in endometrial cancer, held in Milano in December 2014, defined recommendations for diagnosis, surgical procedures, adjuvant treatment, management of locally advanced and metastatic disease. At the CC new risk groups were defined, based on the evaluation of large trials assessing the role of RT in intermediate risk patients and their metanalysis. Through this process, lymphovascular space invasion (LVSI) and grade 3 differentiation were identified as risk factors for nodal recurrence and distant metastasis and were implemented in the definition of the new group of high intermediate risk patients. The results provided by the PORTEC studies (Post Operative Radiation Therapy in Endometrial Cancer) were the basis for the discussion on the role of RT in stage I (PORTEC 1) and the optimal modality of RT between external beam RT (EBRT) and vaginal brachytherapy (VBT) (PORTEC II) while PORTEC III evaluated the role of adjuvant CT with RT in high risk patients. In the ongoing PORTEC IV the value of VBT in high risk stage I is assessed. No data from Phase III studies on the value of combining CT and RT in stage I-II intermediate high risk EC are available even though a combined approach is often part of daily practice. The aim of the ENGOT ENZ_DGCC/EORTC-55102 study is to demonstrate efficacy of adjuvant CT in node negative patients, receiving also VBT, with stage I-II endometrioid grade 3 or stage I-II non endometrioid EC.
In spite of the good preclinical rationales and of the promising initial data no encouraging results have been so far achieved in advanced disease with single agent molecularly targeted agents including mTOR, PI3K, FGFR inhibitors or Bevacizumab.


Current status and future perspectives in the endometrial cancer
Keiichi Fujiwara (Gynecologic Oncology, International Medical Center, Saitama Medical University)
Incidence of endometrial cancer has been increasing dramatically in Japan, and it is the most frequent cancer among the gynecologic malignancies. Since most of endometrial cancer is found at early stage and operable, overall survival is excellent. However, there are several clinically or pathologically high-risk factors such as lymph node metastasis, intraperitoneal spread, or G3 or non-endometrial type histology. In these cases, adjuvant treatment is considered. Although radiation therapy is applied in these occasions in Western countries, chemotherapy is often given in Japan. Pending question for the early stage endometrial cancer is whether we need systemic lymphadenectomy to improve the treatment outcome.
In patients with advanced stage or metastatic or recurrent disease, chemotherapy is the first choice of treatment. Standard chemotherapy regimen for endometrial cancer is a combination of paclitaxel and carboplatin. Target agents such as anti-angiogenesis or mTOR inhibitors are under investigations. To justify the use of target agents, it is essential to conduct translational researches to determine the molecular and/or genetic target for treatment.


Ovarian cancer prevention for women at population risk (No genetic predisposition for ovarian cancer)
Mikio Mikami (Obstetrics and Gynecology, Tokai University Faculty of Medicine)
Epithelial Ovarian Cancer (EOC) has the highest mortality rate out of all types of gynecologic cancer. The overall survival rate for women with EOC has improved marginally in the past 50 years. However, mortality rate of EOC has gradually increased. This is because we cannot detect the disease in its early stages. There is no 'Pap test' that can help us find the changes before they become cancerous. In this review, we will focus EOC prevention for women at population risk, especially on Prophylactic salpingectomy (SAL) and tubal ligation (TL), taking the humble birth control pill and monitoring endometrioma to detect early stage clear cell carcinoma (CCC).
The most compelling theory of EOC carcinogenesis suggests that serous, endometrioid, and CCC are derived from the fallopian tube and the endometrium and not directly from the ovary. By performing SAL when patients undergo an operation during which the fallopian tubes could be removed in addition to the primary surgical procedure (eg, hysterectomy), the risk of EOC may be further reduced. TL has a protective effect specifically against endometrioid and CCC, which supports the theory that these tumors may be due to retrograde menses of endometrial cells. Taking the birth control pill can significantly reduce a woman's risk of EOC. Randomized controlled trials are needed to support the validity of these approach to reduce the incidence of EOC.
CCC which is occupied about 25% among Japanese EOC patients, can arise from endometriosis. Due to the fact that endometriomas are commonly seen in reproductive aged women, usual management includes either conservative surgery or close observation in order to preserve ovarian function. To monitor endometrioma, the identification and development of more accurate clear cell carcinoma diagnostic markers is required.


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